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Focused-ion-beam Milling: A Novel Approach to Probing the Interior of Particles Used for Inhalation Aerosols

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Abstract

Purpose

The current study aimed to examine the pharmaceutical applications of the focused-ion-beam (FIB) in the inhalation aerosol field, particularly to particle porosity determination (i.e. percentage of particles having a porous interior).

Materials and Methods

The interior of various spray dried particles (bovine serum albumin (BSA) with different degrees of surface corrugation, mannitol, disodium cromoglycate and sodium chloride) was investigated via FIB milling at customized conditions, followed by viewing under a high resolution field-emission scanning electron microscope. Two sets of ten particles for each sample were examined.

Results

For the spray-dried BSA particles, a decrease in particle porosity (from 50 to 0%) was observed with increasing particle surface corrugation. Spray-dried mannitol, disodium cromoglycate and sodium chloride particles were determined to be 90–100%, 0–10% and 0% porous, respectively. The porosity in the BSA and mannitol particles thus should be considered for the aerodynamic behaviour of these particles.

Conclusions

The FIB technology represents a novel approach useful for probing the interior of particles linking to the aerosol properties of the powder. Suitable milling protocols have been developed which can be adapted to study other similar particles.

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Acknowledgements

The authors are grateful to Errin Johnson, Toshi Arakawa, Adam Sikorski, Ian Kaplin, Tony Romeo, Emine Korkmaz and Robert Mair of the Electron Microscope Unit (The University of Sydney) for their valuable advice and assistance in the area of microscopy. This work was supported by a grant from the Australian Research Council (ARC Linkage Project LP 0561675 with Nanomaterials Technology Pte. Ltd). DH was a recipient of the Australian Postgraduate Award (Industry).

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Authors and Affiliations

  1. Faculty of Pharmacy, A15, The University of Sydney, NSW 2006, Sydney, Australia

    Desmond Heng, Patricia Tang, Hak-Kim Chan, David J. Cutler & Rania Salama

  2. The Australian Key Centre for Microscopy and Microanalysis, The University of Sydney, NSW 2006, Sydney, Australia

    Julie M. Cairney

  3. Nanomaterials Technology Pte. Ltd., 28 Ayer Rajah Crescent, #03-03, Singapore, 139959, Singapore

    Desmond Heng & Jimmy Yun

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  1. Desmond Heng
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  2. Patricia Tang
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  3. Julie M. Cairney
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Correspondence to Hak-Kim Chan.

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Heng, D., Tang, P., Cairney, J.M. et al. Focused-ion-beam Milling: A Novel Approach to Probing the Interior of Particles Used for Inhalation Aerosols. Pharm Res 24, 1608–1617 (2007). https://doi.org/10.1007/s11095-007-9276-6

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  • DOI: https://doi.org/10.1007/s11095-007-9276-6

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